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Modeling the structure and proton transfer pathways of the mutant His-107-Tyr of human carbonic anhydrase II

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Abstract

We present molecular modeling of the structure and possible proton transfer pathways from the surface of the protein to the zinc-bound water molecule in the active site of the mutant His-107–Tyr of human carbonic anhydrase II (HCAII). No high-resolution structure or crystal structure is available till now for this particular mutant due to its lack of stability at physiological temperature. Our analysis utilizes as starting point a series of structures derived from high-resolution crystal structure of the wild type protein. While many of the structures investigated do not reveal a complete path between the zinc bound water and His-64, several others do indicate the presence of a transient connection even when His-64 is present in its outward conformation. Mutation at the residue 107 also reveals the formation of a new path into the active site. Competing contributions from His-64 sidechain rotation from its outward conformation are also evaluated in terms of optimal path analysis. No indication of a lower catalytic efficiency of the mutant is evident from our results under the condition of thermal stability of the mutant.

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Acknowledgements

The present work has been supported in part by a grant from the Council for Scientific and Industrial Research (CSIR), India.

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  1. Department of Chemistry, Indian Institute of Technology, Kharagpur, 721302, India

    Puspita Halder & Srabani Taraphder

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  1. Puspita Halder
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  2. Srabani Taraphder
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Correspondence to Srabani Taraphder.

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Halder, P., Taraphder, S. Modeling the structure and proton transfer pathways of the mutant His-107-Tyr of human carbonic anhydrase II. J Mol Model 19, 289–298 (2013). https://doi.org/10.1007/s00894-012-1549-2

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